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P085 Morphologic differential diagnosis of juvenile myelomonocytic leukemia (JMML)
S86
Posters
P085 Morphologic differential diagnosis of juvenile myelomonocytic leukemia (JMML) A. Karow ° , C.M. Niemeyer, on behalf of the European Working Group on Childhood MDS (EWOG-MDS). Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany *E-mail: [email protected] Introduction: JMML is a myelodysplastic/myeloproliferative disorder of infancy associated with aberrant Rassignaling due to mutations of PTPN11, RAS, or NF1 genes. Cytogenetic analyses show abnormal karyotype in ~40% of cases with monosomy 7 being the most common abnormality. Clinical and hematological features include splenomegaly, monocytosis, and <20% bone marrow blasts. Viral infections may mimic features of JMML. Aim: To further define the differential diagnosis of JMML. Methods: We screened the EWOG-MDS database for patients with diseases other than JMML in whom the diagnosis JMML was initially suspected based on our own reference morphology. Results: We identified three patients with a clinical and morphological picture of JMML, in whom another diagnosis was later established. The first patient was a 3-year-old boy who presented with otherwise unexplained leuko- and monocytosis, hemorrhage, and infections. However, further analyses demonstrating granulocytic adhesion and chemotaxis defects revealed leukocyte adhesion deficiency (LAD) type 1 syndrome. The second patient was a 3-month-old girl who presented with splenomegaly, leuko- and monocytosis, anemia, and thrombocytopenia and JMML was suspected. However, chest X-ray showed diffuse increase in bone density and infantile malignant osteopetrosis was confirmed by mutation analysis revealing defects of TCIRG1. The third patient was a 10-month-old boy with fatigue, fever, organomegaly, leuko- and monocytosis, and anemia. On reference morphology JMML was suggested. However, he was later diagnosed with endocarditis with intracardiac vegetations on echocardiography. Discussion: Our data illustrate that patients with LAD, osteopetrosis, and severe infections such as endocarditis may present with a clinical and morphological picture of JMML. Experienced morphologists may not be able to distinguish between JMML and these entities without further diagnostic tests such as mutation analysis of PTPN11 and RAS genes. Careful evaluation to rule out a diagnosis of neurofibromatosis type 1, and cytogenetic studies should also be performed.
P086 Flow cytometry in myelodysplastic syndromes: a new tool in the classification and prognostification of low/int-I risk MDS A.A. van de Loosdrecht1 ° , T.M. Westers1 , A.H. Westra1 , A.M. Dr¨ager1 , V.H.J. van der Velden2 , G.J. Ossenkoppele1 . 1 Department of Haematology, VU University Medical Centre, Amsterdam, The Netherlands; 2 Department of Immunology, Erasmus University Medical Centre, Rotterdam, The Netherlands. *E-mail: [email protected] Introduction: The WHO classification contribute to a more refined classification and prognostication of myelodysplastic syndromes (MDS). Flow cytometry (FC) may add diagnostic and prognostic criteria to discriminate RA from RCMD (± ring sideroblasts; [RS]). Methods: We developed a 4-colour FC procedure that recognises all differentiation stages of granulocytic and monocytic lineages in normal bone marrow (BM). Results: In 50 newly diagnosed MDS patients (RA, RARS, RCMD, RCMD-RS, MDS-U, RAEB-1/2) BM samples, aberrant expression of differentiation antigens were demonstrated in 1 or more lineages. FC identified aberrancies in granulopoiesis and monocytopoiesis in 94% of the cases. In the majority of cases abnormal relations between CD13, CD16, CD11b, CD15 and HLA-DR were prominent in the granulopoiesis. In 34% of the cases a striking monocytopenia and in 59% abnormal surface expression of CD14, CD36 was found. In 38% of the cases lineage infidelity antigen expression was detectable (coexpression of CD5, CD7, CD19 or CD56 on CD34+ myeloid blasts). In patients with RA+/−RS and MDS-U, additional FC aberrancies were identified including lineage infidelity Ag expression on myeloid blasts in 30% of the cases. A significant increase in the MDS dysplasia flow-score among WHO subgroups from RA+/−RS, RCMD+/−RS to RAEB1/2 was measured. No significant differences were seen between the MDS dysplasia flow-score and WHOcytogenetic subgroups and IPSS. A significant increased MDS dysplasia flow-score was observed between nontransfusion dependent patients and patients in progression to advanced MDS. In only 1/19 non-transfusion dependent patients an infidelity marker on myeloid blasts could be observed. In contrast, 14/24 patients with transfusiondependency and/or in progressive disease, infidelity markers on myeloid blasts were detected. Within the pure-RA+/−RS subgroup only patients with infidelity marker expression on myeloid blasts were transfusion dependent. Discussion: It is concluded that FC in MDS identifies aberrancies in the granulocytic and monocytic lineages and classifies patients with multilineage aberrancies not otherwise determined by cytology (WHO). FC may discriminate pure RA from FC-defined RCMD. FC identifies patients at risk for transfusion dependency and/or
Posters
P085 Morphologic differential diagnosis of juvenile myelomonocytic leukemia (JMML) A. Karow ° , C.M. Niemeyer, on behalf of the European Working Group on Childhood MDS (EWOG-MDS). Pediatric Hematology and Oncology, Department of Pediatrics and Adolescent Medicine, University of Freiburg, Freiburg, Germany *E-mail: [email protected] Introduction: JMML is a myelodysplastic/myeloproliferative disorder of infancy associated with aberrant Rassignaling due to mutations of PTPN11, RAS, or NF1 genes. Cytogenetic analyses show abnormal karyotype in ~40% of cases with monosomy 7 being the most common abnormality. Clinical and hematological features include splenomegaly, monocytosis, and <20% bone marrow blasts. Viral infections may mimic features of JMML. Aim: To further define the differential diagnosis of JMML. Methods: We screened the EWOG-MDS database for patients with diseases other than JMML in whom the diagnosis JMML was initially suspected based on our own reference morphology. Results: We identified three patients with a clinical and morphological picture of JMML, in whom another diagnosis was later established. The first patient was a 3-year-old boy who presented with otherwise unexplained leuko- and monocytosis, hemorrhage, and infections. However, further analyses demonstrating granulocytic adhesion and chemotaxis defects revealed leukocyte adhesion deficiency (LAD) type 1 syndrome. The second patient was a 3-month-old girl who presented with splenomegaly, leuko- and monocytosis, anemia, and thrombocytopenia and JMML was suspected. However, chest X-ray showed diffuse increase in bone density and infantile malignant osteopetrosis was confirmed by mutation analysis revealing defects of TCIRG1. The third patient was a 10-month-old boy with fatigue, fever, organomegaly, leuko- and monocytosis, and anemia. On reference morphology JMML was suggested. However, he was later diagnosed with endocarditis with intracardiac vegetations on echocardiography. Discussion: Our data illustrate that patients with LAD, osteopetrosis, and severe infections such as endocarditis may present with a clinical and morphological picture of JMML. Experienced morphologists may not be able to distinguish between JMML and these entities without further diagnostic tests such as mutation analysis of PTPN11 and RAS genes. Careful evaluation to rule out a diagnosis of neurofibromatosis type 1, and cytogenetic studies should also be performed.
P086 Flow cytometry in myelodysplastic syndromes: a new tool in the classification and prognostification of low/int-I risk MDS A.A. van de Loosdrecht1 ° , T.M. Westers1 , A.H. Westra1 , A.M. Dr¨ager1 , V.H.J. van der Velden2 , G.J. Ossenkoppele1 . 1 Department of Haematology, VU University Medical Centre, Amsterdam, The Netherlands; 2 Department of Immunology, Erasmus University Medical Centre, Rotterdam, The Netherlands. *E-mail: [email protected] Introduction: The WHO classification contribute to a more refined classification and prognostication of myelodysplastic syndromes (MDS). Flow cytometry (FC) may add diagnostic and prognostic criteria to discriminate RA from RCMD (± ring sideroblasts; [RS]). Methods: We developed a 4-colour FC procedure that recognises all differentiation stages of granulocytic and monocytic lineages in normal bone marrow (BM). Results: In 50 newly diagnosed MDS patients (RA, RARS, RCMD, RCMD-RS, MDS-U, RAEB-1/2) BM samples, aberrant expression of differentiation antigens were demonstrated in 1 or more lineages. FC identified aberrancies in granulopoiesis and monocytopoiesis in 94% of the cases. In the majority of cases abnormal relations between CD13, CD16, CD11b, CD15 and HLA-DR were prominent in the granulopoiesis. In 34% of the cases a striking monocytopenia and in 59% abnormal surface expression of CD14, CD36 was found. In 38% of the cases lineage infidelity antigen expression was detectable (coexpression of CD5, CD7, CD19 or CD56 on CD34+ myeloid blasts). In patients with RA+/−RS and MDS-U, additional FC aberrancies were identified including lineage infidelity Ag expression on myeloid blasts in 30% of the cases. A significant increase in the MDS dysplasia flow-score among WHO subgroups from RA+/−RS, RCMD+/−RS to RAEB1/2 was measured. No significant differences were seen between the MDS dysplasia flow-score and WHOcytogenetic subgroups and IPSS. A significant increased MDS dysplasia flow-score was observed between nontransfusion dependent patients and patients in progression to advanced MDS. In only 1/19 non-transfusion dependent patients an infidelity marker on myeloid blasts could be observed. In contrast, 14/24 patients with transfusiondependency and/or in progressive disease, infidelity markers on myeloid blasts were detected. Within the pure-RA+/−RS subgroup only patients with infidelity marker expression on myeloid blasts were transfusion dependent. Discussion: It is concluded that FC in MDS identifies aberrancies in the granulocytic and monocytic lineages and classifies patients with multilineage aberrancies not otherwise determined by cytology (WHO). FC may discriminate pure RA from FC-defined RCMD. FC identifies patients at risk for transfusion dependency and/or